We have recently isolated a small chondroitin/dermatan sulfate proteoglycan Epiphycan from fetal bovine epiphyseal cartilage. Amino acid sequencing of peptides generated from the core protein suggest that this proteoglycan is the mammalian homolog to the chicken PG-Lb. A cDNA library has been constructed from isolated fetal cartilage mRNA and used as a template to PCR amplify segments of bovine Epiphycan cDNA. When these segments were cloned into the Bluescript vector and sequenced, the relation to chicken PG-Lb was confirmed and demonstrated that Epiphycan is a unique mammalian proteoglycan which is structurally closely related to but distinct from Osteoglycin. Epiphycan is also related to the proteoglycans Decorin and Biglycan. These observations form the basis for the current proposal where we plan to (a) structurally analyze Epiphycan isolated from fetal bovine epiphyseal cartilage (b) clone and characterize cDNA's from bovine and mouse encoding the corresponding core protein (c) determine the tissue distributions of Epiphycan and other related molecules during embryonic development in mouse tissues (d) identify and characterize the interaction of Epiphycan with different types of collagen (e) isolate and characterize the mouse Epiphycan gene and (f) evaluate the importance of Epiphycan by generating transgenic mice in which the Epiphycan gene has been eliminated. These mice will subsequently be characterized as to the importance of Epiphycan in bone and cartilage development.